The candidate, Dr. Lakshmi Devi holds a Ph.D. degree from the University of Windsor, Canada and is an Associate Professor in the Department of Pharmacology at the New York University School of Medicine. She is currently funded by an independent grant support from NIDA-NIH-DA 06683 to study posttranslational regulation of opioid receptors. The long-term career goal is to become an established independent investigator at the forefront of studies on the molecular basis of drug addiction. New York University School of Medicine provides the intellectual environment for synergistic and collaborative interactions necessary for the development of a strong research program. The Independent Service Award will facilitate this by relieving considerable amount of teaching and administrative duties. This plan has the full support of the Department of Pharmacology and of the School. The focus of studies in the laboratory is to explore molecular mechanisms that modulate opioid receptor function. The exposure to opioid peptides or opiate alkaloids initiates a biological response by opioid receptors. Continuous or repeated exposure to opioids causes decreased sensitivity to the drug; this desensitization response is regulated by multiple mechanisms. Acute opioid treatment results in rapid desensitization without the loss of receptor number whereas, chronic opioid treatment results in longer desensitization due to a net loss of receptors from the cell. Relatively little is known about the molecular mechanisms underlying these events. The objective of studies proposed in this grant application is to explore novel mechanisms such as internalization and dimerization that modulate opioid receptor function. The specific aims are: (i) to explore opioid receptor trafficking (ii) to explore the role of dimerization in opioid receptor function and (iii) to characterize heterodimerization between opioid receptor types. The studies described in this grant application will provide critical information on early events that modulate opioid receptor function. Elucidation of the cellular pathways involved in modulation of receptor function is a compelling strategy for identifying appropriate pharmacological interventions for drug addiction.